Kim Sun H, Nikolics Lilla, Abbasi Fahim, Lamendola Cindy, Link James, Reaven Gerald M, Lindley Steven
Department of Medicine, 300 Pasteur Drive, S025, Stanford, CA 94305-5103, USA.
J Psychiatr Res. 2010 Jun;44(8):493-8. doi: 10.1016/j.jpsychires.2009.11.007. Epub 2009 Dec 3.
Second generation antipsychotics (SGAs) can increase weight gain and weight-induced insulin resistance. Recent studies have suggested weight-independent effects of certain SGAs on insulin resistance; however the magnitude of these effects and the relationship between BMI and insulin resistance in patients on SGAs are not established. To evaluate, the relationship between body mass index (BMI) and insulin resistance in 54 patients being stably treated with olanzapine (n=19), risperidone (n=16), or aripiprazole (n=19) was compared with data from a large reference population (n=201) not on SGAs. Insulin resistance was directly quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. The relationship between BMI and SSPG was similar between the SGA (r=0.58) and the reference population (r=0.50). When SSPG was standardized based on expected values for the reference population, patients on olanzapine had a higher degree of insulin resistance (mean z-score+/-SD, 0.68+/-0.9) than expected for level of BMI compared with those on aripiprazole (-0.25+/-1) and risperidone (-0.3+/-0.9), F(2,51)=6.28 (p=0.004). Thus, olanzapine group was 0.76 SD above the reference population or in the 78 percentile for insulin resistance. SSPG was correlated with fasting plasma insulin concentration (0.78 (0.64-0.87), p<0.001) but not fasting glucose concentration (0.15 (-0.13-0.40), p=0.29). In conclusion, BMI contributes a quarter to a third of the variance in insulin resistance in the SGA population similar to the reference population. Olanzapine also appears to have an independent effect on insulin resistance that is above and beyond obesity.
第二代抗精神病药物（SGAs）可增加体重并导致体重相关的胰岛素抵抗。近期研究提示某些SGAs对胰岛素抵抗存在与体重无关的效应；然而这些效应的程度以及服用SGAs患者的体重指数（BMI）与胰岛素抵抗之间的关系尚未明确。为进行评估，将54例稳定服用奥氮平（n = 19）、利培酮（n = 16）或阿立哌唑（n = 19）的患者的BMI与胰岛素抵抗之间的关系，与来自未服用SGAs的大型对照人群（n = 201）的数据进行比较。通过在胰岛素抑制试验期间测量稳态血浆葡萄糖（SSPG）浓度直接定量胰岛素抵抗。SGAs组（r = 0.58）与对照人群（r = 0.50）中BMI与SSPG之间的关系相似。当根据对照人群的预期值对SSPG进行标准化时，与服用阿立哌唑（-0.25±1）和利培酮（-0.3±0.9）的患者相比，服用奥氮平的患者具有高于BMI水平预期的胰岛素抵抗程度（平均z评分±标准差，0.68±0.9），F(2,51)=6.28（p = 0.004）。因此，奥氮平组比对照人群高出0.76个标准差，或在胰岛素抵抗的第78百分位数。SSPG与空腹血浆胰岛素浓度相关（0.78（0.64 - 0.87），p<0.001），但与空腹血糖浓度无关（0.15（-0.13 - 0.40）），p = 0.29）。总之，与对照人群相似，BMI在SGAs人群中对胰岛素抵抗方差的贡献为四分之一至三分之一。奥氮平似乎对胰岛素抵抗也有独立于肥胖之外的作用。
